真核细胞内，U1 snRNP的经典功能是参与外显子剪接。近年来对U1 snRNP非经典功能的研究发现，它可以在转录组规模抑制内含子内的mRNA 3’末端剪切加poly(A)尾过程而维持全长mRNA转录的完整性，但其具体的分子机制未知。我们前期结果发现，U1 snRNA/pre-mRNA稳定结合在此过程中发挥重要的作用。本计划书围绕这一新的普遍的分子生物学现象，进一步研究其作用机制和生物学意义，包括：(1) U1 snRNP如何抑制mRNA3’末端加工的剪切步骤而维持下游转录完整性；（2）U1 snRNP调控的内含子poly(A)位点加工产物在细胞内能否普遍形成成熟的mRNA,而翻译成蛋白质；（3）若条件允许，探讨U1的这一功能是否参与人胚胎干细胞神经分化过程。本计划书的实施，有助于拓展基因转录后调控理论的前沿，和解决mRNA加工领域内重难点问题。

U1 snRNP is well-known for its function in mRNA splicing by base-pairing to the 5'-splicing site (5'-SS) in eukaryotic cells. It is increasingly appreciated that U1 snRNP could also function in preventing premature cleavage and polyadenylation (PCPA) to protect mRNA integrity. However, the molecular mechanisms underlying this basic biological phenomenon still remain elusive. Our preliminary data showed that the stable association of U1 snRNA with pre-mRNA plays a leading role in this process. Here we propose to further investigate the mechanisms and biological significance of this new phenomenon. Specifically, we wish to focus on following questions: (1) How U1 snRNP inhibits the cleavage step of mRNA 3' processing to protect mRNA integrity during transcription? (2) Whether the truncated form of mRNA whose 3' processing is regulated by U1 snRNP, could be generally translated into functional proteins in cells? (3) If conditions permit, we will investigate whether this U1's novel role is involved in the process of neural differentiation of hESCs. We believe the execution of this proposal will expand the horizon of basic theory of post-transcriptional gene regulation, and address several important questions in mRNA processing field.